|
Basic Characteristics of Mutations
|
|
Mutation Site
|
N155D |
|
Mutation Site Sentence
|
Thirty-two additional non-polymorphic mutations that occurred in five or more INSTI-treated persons were significantly selected by INSTI therapy (corrected P value ≤0.05), including four mutations at established INSTI-resistance positions (H51D, E92A, Q95R and N155D) and one mutation (N142T) in the highly conserved catalytic loop extending between positions 140 and 149 (Table 4). |
|
Mutation Level
|
Amino acid level |
|
Mutation Type
|
Nonsynonymous substitution |
|
Gene/Protein/Region
|
IN |
|
Standardized Encoding Gene
|
gag-pol:155348
|
|
Genotype/Subtype
|
HIV-1 |
|
Viral Reference
|
-
|
|
Functional Impact and Mechanisms
|
|
Disease
|
HIV Infections
|
|
Immune
|
- |
|
Target Gene
|
-
|
|
Clinical and Epidemiological Correlations
|
|
Clinical Information
|
- |
|
Treatment
|
INSTIs |
|
Location
|
- |
|
Literature Information
|
|
PMID
|
31617907
|
|
Title
|
Integrase strand transfer inhibitor (INSTI)-resistance mutations for the surveillance of transmitted HIV-1 drug resistance
|
|
Author
|
Tzou PL,Rhee SY,Descamps D,Clutter DS,Hare B,Mor O,Grude M,Parkin N,Jordan MR,Bertagnolio S,Schapiro JM,Harrigan PR,Geretti AM,Marcelin AG,Shafer RW
|
|
Journal
|
The Journal of antimicrobial chemotherapy
|
|
Journal Info
|
2020 Jan 1;75(1):170-182
|
|
Abstract
|
BACKGROUND: Integrase strand transfer inhibitors (INSTIs) are expected to be widely adopted globally, requiring surveillance of resistance emergence and transmission. OBJECTIVES: We therefore sought to develop a standardized list of INSTI-resistance mutations suitable for the surveillance of transmitted INSTI resistance. METHODS: To characterize the suitability of the INSTI-resistance mutations for transmitted HIV-1 drug resistance (TDR) surveillance, we classified them according to their presence on published expert lists, conservation in INSTI-naive persons, frequency in INSTI-treated persons and contribution to reduced in vitro susceptibility. Mutation prevalences were determined using integrase sequences from 17302 INSTI-naive and 2450 INSTI-treated persons; 53.3% of the INSTI-naive sequences and 20.0% of INSTI-treated sequences were from non-B subtypes. Approximately 10% of sequences were from persons who received dolutegravir alone or a first-generation INSTI followed by dolutegravir. RESULTS: Fifty-nine previously recognized (or established) INSTI-resistance mutations were present on one or more of four published expert lists. They were classified into three main non-overlapping groups: 29 relatively common non-polymorphic mutations, occurring in five or more individuals and significantly selected by INSTI treatment; 8 polymorphic mutations; and 22 rare mutations. Among the 29 relatively common INSTI-selected mutations, 24 emerged as candidates for inclusion on a list of INSTI surveillance drug-resistance mutations: T66A/I/K, E92G/Q, G118R, F121Y, E138A/K/T, G140A/C/S, Y143C/H/R/S, S147G, Q148H/R/K, N155H, S230R and R263K. CONCLUSIONS: A set of 24 non-polymorphic INSTI-selected mutations is likely to be useful for quantifying INSTI-associated TDR. This list may require updating as more sequences become available from INSTI-experienced persons infected with HIV-1 non-subtype B viruses and/or receiving dolutegravir.
|
|
Sequence Data
|
-
|
|
|